1. The Field of the Invention
The present invention relates to compositions for decontaminating skin exposed to capsaicinoid and/or other chemical irritants. More particularly, the present invention relates to compositions for cleansing capsaicinoids from the skin, inactivating capsaicinoid receptors, and treating or otherwise mitigating the physiological responses associated with capsaicinoid exposure and receptor activation.
2. The Relevant Technology
Capsaicinoids are a group of pungent natural products that are isolated from the dried fruits of chili peppers (e.g., Capsicum frutescens) via extraction such as with an organic solvent. The crude extract of peppers is called Oleoresin Capsicum (“OC”) and contains a diverse variety of chemicals including significant quantities of the capsaicinoids. There are six naturally occurring capsaicinoid analogues (shown in FIG. 1) that vary in concentration in peppers and OC: capsaicin (8-methyl-N-vanillyl-trans-6-nonenamide) (35-55%); dihydrocapsaicin (8-methyl-N-vanillylnonaneamide) (30-50%); nordihydrocapsaicin (5-10%); nonivamide (n-vanillynonanamide) (<5%), homocapsaicin (1-5%); i and homodihydrocapsaicin (1-5%).
Hotter peppers (e.g., jalapeños) typically rated with higher Scoville Heat Unit values (“SHU”) contain higher concentrations of capsaicin and dihydrocapsaicin than sweeter peppers (e.g., bell peppers) that contain only small quantities of dihydrocapsaicin and the other minor and less potent capsaicinoid analogues. Nonivamide (i.e., PAVA, VP, and Capsaicin II) has traditionally been referred to as synthetic capsaicin because of its facile laboratory synthesis and frequency of use as a surrogate for OC or crystalline capsaicinoid mixtures, but it has also been shown to be a natural product. Other structural analogues of nonivamide may also be used as surrogates for OC and will typically consist of a shorter or longer alkyl chain variants (e.g., heptyl, octyl decyl, etc). Both the aromatic vanilloid ring (3-OH-4-MeO-benzylamide) portion and the aliphatic chain (between 8-12 carbon atoms) are required for optimum pharmacological activity (e.g., activation of TRPV1, pain, etc.).
For centuries humans have used hot peppers, extracts, and capsaicinoids for a variety of purposes including traditional homeopathic treatment of various malaises such as dental pain, neuropathic pain, arthritis, stomach discomfort, antimicrobial defense, algesia, and as an aphrodisiac. Currently, cayenne pepper products and topical creams containing capsaicinoids are sold over-the-counter (“OTC”) as dietary supplements and treatments to aid in digestion, stimulate metabolism and weight loss, and to help alleviate acute and chronic pain associated with acute injury, chronic inflammation, and neurogenic pain (e.g., Capzacin HP, Zostrix, Axsain, etc.). It has been reported that as early as 1850 dentists used alcoholic pepper extracts as an oral analgesic.
OC and capsaicinoids have also gained popularity as the active components for the production of self-defense weaponry known as less-than-lethal pepper spray products used by law enforcement and postal service employees as well as civilians. The products are used by law enforcement agencies worldwide to assist in the apprehension of non-compliant suspects and in crowd control. Postal workers and the general public also carry these products to help protect themselves against aggressive attack by animals and other individuals. A recent variation of the traditional pepper spray is the use of friable projectiles, which are similar to paint balls and contain inert powder mixed with crystalline capsaicinoids as the crowd/suspect control agent. Some of the earliest documented uses of hot peppers and capsaicinoids as a means of self-defense date back to the Mayans who reportedly burned pepper plants to help ward off attacks.
Currently, a variety of pepper spray products are available to law enforcement personnel and the general public. These products vary in size, shape, labeling, etc. Regardless of these differences, many of these products are similar in their composition. The vast majority of pepper spray devices are prepared using OC, which is the concentrated oil obtained from extraction of hot peppers. This is a crude extract from peppers, containing hundreds to thousands of different chemicals that vary in concentration from extract to extract, each possessing their own pharmacological and toxicological profiles. This extract is also the source for high concentrations of the capsaicinoids, the bioactive chemicals in pepper spray devices that are responsible for the irritant and pain producing properties characteristic of pepper spray products. Non-OC-based products typically consist of nonivamide (e.g., <2% w/v).
OC-based and non-OC-based pepper spray products are relatively simple. The solution for these products can be prepared by simple dilution of food-grade OC, approximately 5-100-fold (e.g., 1-20% v/v OC), using various solvents such as water, isopropyl or ethyl alcohol, other alcohols, propylene glycol, freons (e.g., CFC's), other organic solvents (e.g., TCE), or combinations of these substances. These dilute OC solutions are packaged in canisters and pressurized using a gaseous substance, such as air, nitrogen, carbon dioxide, propane, isobutane, combinations thereof, and the like. Some manufacturers have employed a highly volatile solvent system to prepare their products, and, thus, the solvent also serves as the propellant by maintaining pressure in the canister by solvent evaporation to form a gas. Typical OC-based pepper spray devices can be effectively dispensed between 5 to 20 times using sequential 1-second pulses from a range of 5-30 ft, depending upon the product and environmental conditions.
Pepper spray weapons are designed to deliver concentrated solutions of capsaicinoids to the eyes, skin and respiratory tract. When pepper sprays are used, the capsaicinoids present in the product activate TRPV1 (i.e., the capsaicin receptor, VR1) and possibly other sensory receptors and cause the characteristic physiological effects described below. The overall intended effects are temporary and safe incapacitation of the subject through pain, temporary blindness, disorientation, and compromised respiration.
There are many factors that can influence the performance and safety of pepper spray devices including the strength and characteristics of the capsaicinoid solution, as well as the efficiency and accuracy of delivery of the product. It has recently been shown that the vehicle composition of the product drastically influenced absorption of capsaicinoids into skin (i.e., stratum corneum) and into the dermis where sensory nerves dictate the pharmacodynamics of these products. Individual differences in sensitivity to the capsaicinoids, tolerance, case-specific differences (e.g., drug use, goal orientation, and altered mental status), and environmental conditions (e.g., space, ventilation, and wind) can also influence the performance and safety of these products. In general, however, the most important determinant of product efficacy and safety is the amount of capsaicinoids delivered to the targeted subject.
Recent research has demonstrated significant variability in the concentrations of capsaicinoids in OC-based pepper spray products. Representative manufactures of OC-based pepper spray products include First Defense, Defense Technologies, Guardian Personal Security Products, Inc., Security Plus, AERKO International, DMA, Mace Security International, Inc., Guardian Protective Devices, ChemArmor, Counter Assault Tactical Systems, UDAP Industries, and others. Analysis of multiple, randomly-selected commercial pepper spray products used by law enforcement personnel and the general public has demonstrated that the concentration of capsaicinoids in these products varied up to 100-fold. In addition, this variability was independent of the brand name, manufacturer, labeled SHU rating, and % OC listed on the canister. In other words, not all 10% OC products that were rated at 2 million SHU were equal in strength. In fact, one manufactured product that purportedly contained only 5% OC at 2 million SHU contained much higher concentrations of capsaicinoids than some of the 10% OC sprays also rated at 2 million SHU, and two manufactured 10% OC sprays were visibly much different in color and varied significantly in their concentrations of active ingredients despite the canisters having identical labels and origins. These studies demonstrated that the actual potency for many pepper spray products, as represented by labeled % OC and SHU value, was not representative of the true strength of the product. Such differences in the concentration of active ingredients may be a major contributing factor for the variability in performance and safety of these products.
Capsaicinoids selectively interact with TRPV1 (i.e., capsaicin receptor, VR1) or other sensory receptors to promote a complex array of physiological effects. Many of these effects are initiated through the initial stimulation of capsaicinoid receptors to promote massive increases in cytosolic calcium and sodium ions. This initial process initiates neuronal action potentials to produce the immediate sensation of pain and burning, elicits behavioral responses, as well as complex sequences of events within cells and the surrounding tissues including the release of substance P, CGRP, Neurokinin A and other pro-inflammatory substances and neuropeptides that mediate pain perception, irritation, and inflammation of the exposed sites. Although strategies to block the effects of substance P and NK1 receptors and the capsaicinoid receptors have been proposed as pain treatments, they are not practical due to limitations in drug delivery, stability, specificity, and availability. Additionally, an effective means of treating or preventing the physiological effects that arise from capsaicinoid exposure has not yet been provided. While the use of capsaicinoids has increased, there remains a need for a product to effectively cleanse and decontaminate sites of capsaicinoid exposure.
Therefore, it would be advantageous to have compositions capable of cleansing and/or decontaminating subjects that have been exposed to capsaicinoids through various commercial products. More particularly, it would be beneficial to be able to treat, mitigate, or prevent the undesirable physiological effects associated with capsaicinoid exposure.